Project Description: Heart failure is a growing public health problem with high mortality and morbidity. The concept of preclinical heart failure is based on the fact that abnormal heart structure/function can be detected by complementary methods before the development of symptoms. Patients with those abnormalities may progress to symptomatic heart failure and are at increased risk of adverse cardiac events. This human translational project aims to develop novel therapeutics by maximizing the cGMP system using two FDA approved medications, Nesiritide and Tadalafil. to improve renal function patients with preclinical heart failure. Our goals are to further our understanding the cGMP pathway in the mechanism of renal dysfunction in preclinical heart failure and to develop therapies to improve the renal function with the hope of delaying the progression of preclinical heart failure to symptomatic heart failure.